The proposed studies are designed to gain an understanding of the manner in which granulopoiesis is regulated, and in particular the role that vascular endothelium may play in this regulation. Utilizing short term endothelial cell cultures, we plan to evaluate the kinetics of granulocyte-monocyte-macrophage colony-stimulating activity (CSA) pro-duction by both human and murine endothelium. We will study the cell types upon which endothelial CSA acts, and will characterize this activity both functionally and biochemically. We will also evaluate the effect on endothelial CSA production of a number of manipulations or substances known to affect either endothelial cell function, serum CSA levels or in-vivo granulopoiesis. More specifically in our initial experiments, we will begin or extend studies on the role of interactions of monocytes, lymphocytes and granulocytes with the endothelium and the effects of endotoxin, granulocyte derived colony inhibiting activity, indomethacin and angiotensin II on endothelial CSA production. During the course of this work we will compare monocyte derived CSA to that derived from endothelial cells, and evaluate endothelium for the production of both erythropoietic and thrombopoietic substances.